[Clinical case - neoplasm of the nasal septum, which turned out to be papillary cancer of the ectopic thyroid gland]. / Klinicheskii sluchai ­ novoobrazovanie peregorodki nosa, okazavsheesya papillyarnym rakom ektopirovannoi shchitovidnoi zhelezy.

In this clinical case, papillary carcinoma was detected in the ectopic area of the thyroid gland in the presence of an unchanged thyroid gland of natural localization. An extremely rare disease is presented and an examination algorithm is proposed that is recommended to exclude unusual pathology in the absence of a response to ongoing conservative treatment.

[Safety and efficacy of a new method of percutaneous nephrolithotripsy performed under ultrasound and endovisual control without the use of intraoperative x-ray examination].

PURPOSE OF THE STUDY: to study the safety and efficacy of using a new method of performing percutaneous nephrolithotripsy under ultrasound and endovisual control. MATERIALS AND METHODS: A comparative analysis of the results of percutaneous nephrolithotripsy performed under ultrasound and endovisual control in 515 (84.1%) patients (main group) and percutaneous nephrolithotripsy performed under fluoroscopic control in 97 (15.8%) patients (control group) was carried out. The groups did not differ in age, gender, body mass index, the number and location of stones, and the duration of the disease. In the main group, there were more patients with large, staghorn and X-ray negative stones, and there were also more patients with kidney block. To analyze and stratify the complications of percutaneous nephrolithotripsy, we used a modified classification of surgical complications according to the Clavien-Dindo system. Statistical analysis of the material was carried out using the licensed package IBM SPSS Statistics Version 14.0.1. RESULTS: The average duration and number of stages of operations in the main and control groups was the same. Almost all operations in groups (93,8% 91,8%) were performed in one step (=0,55). In the main group, in the vast majority of cases95,1%; <0,001), percutaneous nephrolithotripsy was performed through one puncture access, with the degree of complete elimination of stones statistically the same as in the control group (80.6% in the main group and 70.1% in the control group, p=0.158). The degree of decrease in hemoglobin in the postoperative period in the groups did not differ (=0,271). The frequency of postoperative complications in both groups did not differ statistically: in the control - 33.0%; in the main group - 29.3% (p=0.469). The severity of complications according to Clavien-Dindo did not differ in the groups either (p=0.17). CONCLUSION: Percutaneous nephrolithotripsy under ultrasound and endovisual control is a safe and effective operation. The results of the operation and the frequency of early complications are comparable with the traditional X-ray control technique.

Rituximab and Abatacept Are Effective in Differential Treatment of Interstitial Lymphocytic Lung Disease in Children With Primary Immunodeficiencies.

Background: Interstitial lymphocytic lung disease (ILLD), a recently recognized complication of primary immunodeficiencies (PID), is caused by immune dysregulation, abnormal bronchus-associated lymphoid tissue (BALT) hyperplasia, with subsequent progressive loss of pulmonary function. Various modes of standard immunosuppressive therapy for ILLD have been shown as only partially effective. Objectives: To retrospectively evaluate the safety and efficacy of abatacept or rituximab in treatment of ILLD in children with PID. Methods: 29 children (median age 11 years) with various forms of PID received one of the two therapy regimens predominantly based on the lesions' immunohistopathology: children with prevalent B-cell lung infiltration received rituximab (n = 16), and those with predominantly T-cell infiltration received abatacept (n = 17). Clinical and radiological symptoms were assessed using a severity scale developed for the study. Results: The targeted therapy with abatacept (A) or rituximab (R) enabled long-term control of clinical (A 3.4 ± 1.3 vs. 0.6 ± 0.1; R 2.8 ± 1 vs. 0.7 ± 0.05, p < 0.01) and radiological (A 18.4 ± 3.1 vs. 6.0 ± 2.0; R 30 ± 7.1 vs. 10 ± 1.7, p < 0.01) symptoms of ILLD in both groups and significantly improved patients' quality of life, as measured by the total scale (TS) score of 57 ± 2.1 in treatment recipients vs. 31.2 ± 1.9 before therapy (p < 0.01). Conclusions: ILLD histopathology should be considered when selecting treatment. Abatacept and rituximab are effective and safe in differential treatment of ILLD in children.

[The development of laboratory diagnostic of leprosy using polymerase chain reaction].

The purpose of study is to develop techniques of laboratory diagnostic of leprosy on the basis of polymerase chain reaction. The techniques were worked through such as extraction of DNA from various clinical material (bioptates and scarifcate of skin, scrapes from mucous surface of nose and trophic ulcers, blood serum). The systems of oligonucleotides were constructed to 16S pRNA and probe for identifcation of Mycobacterium leprae in real-time format for amplifer DT-96 ("The DNA-Technology", Russia). The optimal regimen of amplifcation was worked out. To control polymerase chain reaction processing a system of internal control was introduced. The evaluation of specifcity of test-system was implemented using 17 strains of various types of mycobacteria and clinical samples from 32 patients with leprosy and 15 healthy individuals being in family contact with patients with leprosy. The 100% sensitivity was established concerning detection of Mycobacterium leprae in bioptates of skin using polymerase chain reaction technique as compared with standard bacterioscopic technique (88.9%). In all other clinical samples, a higher sensitivity of developed test-system on the basis of polymerase chain reaction was detected too. The proposed test-system has higher sensitivity and specifcity that permits to resolve an issue of fast identifcation of Mycobacterium leprae. It can be applied in epidemiological studies at investigation of prevalence of agent of disease.

DMSO-Free Cryopreservation of Human Umbilical Cord Tissue.

Human umbilical cord represents a source of multipotent stromal cells of a supreme therapeutic potential. The cells can be isolated from either fresh or cryopreserved umbilical cord tissues. DMSO is a cryoprotectant most commonly used for preservation of umbilical cord tissues; however, cyto- and genotoxicity of this compound is evident and well documented. In the present study we performed successful cryopreservation of the umbilical cord tissue using other cryoprotectants: propylene glycol, ethylene glycol, and glycerol. Of these, 1.5 M ethylene glycol and 20% glycerol turned out to be the best in terms of the preservation of living cells within the frozen tissue, early onset of migration of these cells out of the thawed explants, and overall efficacy of multipotent stromal cell isolation. Cryobanking of tissues can improve availability of multiple cell products for medical purposes and promote the development of personalized medicine.

Association of polymorphisms of HLA-DRB1 and TNF-308 G/A with radiographic joint damage in patients with early rheumatoid arthritis with high inflammatory activity, treated according to the principle of "Treat to target" (REMARKA study).

AIM: To clarify the association between HLA-DRB1 and TNFα (-308G>A) genes polymorphism and joint destruction/further progression during 12 months of the follow-up period (FUP) in patients with early (<6 months), active, predominantly antibodies to cyclic citrullinated peptide (ACCP) and rheumatoid factor (RF)-positive rheumatoid arthritis (RA) treated according to "Treat to target" strategy. MATERIALS AND METHODS: The study included 85 patients with early RA and duration of symptoms <6 months. All patients were initially assigned to subcutaneous methotrexate (MTX) with rapid dose escalation to 20-25 mg/week. Combination MTX + biological therapy, mainly adalimumab, was used when MTX was ineffective. Joint destruction was assessed by Sharp-Van der Heijde modification scoring method at baseline and after 12 months FUP. Real time polymerase chain reaction (PCR-RT) was used for TNFα gene polymorphism (-308G>A) genotyping. Low resolution PCR-RT with subsequent sequence-based typing of *04 were performed to study HLA-DRB1 gene polymorphism. The HLA-DRB1*01, *04:01, *04:04, *04:05, *04:08, *10 alleles were categorized as SE+ (Shared Epitope) alleles. RESULTS: As for TNFα gene polymorphism, it was demonstrated that the number of narrowings and total Sharp score values were almost twice as high at baseline in GG genotype carriers as compared to GA genotype carriers (р<0,005, and р<0,004 respectively). Similar association was found after 12mo FUP. The progression of joint destruction, assessed as the change (∆) in the number of erosions, joint space narrowings and the total score, was statistically significantly associated with HLA-DRB1*(SE) genotypes: the carriers of SE (SE+/SE+) double-dose had more advanced progression as compared to (SE+/SE-)/(SE-/SE-) carriers (р<0,028, р<0,019, р<0,035 respectively). CONCLUSION: Our data suggest that HLA-DRB1 (SE+) gene and TNFα (-308G>A) polymorphisms are associated with the progression of radiographic joint destruction in early, active RA patients managed according to "Treat to target" stratagy.

[Microbiological analysis as effective tool for optimization of empirical antibiotic therapy in the urological clinic].

AIM: to study the features of microbiota in patients of urological departments and to optimize the schemes of antibiotic therapy. MATERIALS AND METHODS: Data of microbiological studies in patients of urological departments in 2017 years were analyzed. Isolation of pathogens was carried out using standard techniques. A disk diffusion test using Mueller-Hinton agar with BioRad disks was used to determine the sensitivity. The statistical analysis was performed using the WHONET 5.4 program. In addition, a comparison with the results of the PCR study was done. RESULTS: A total of 672 etiological pathogens were isolated in whole clinic in 2017 year. From those, 173 pathogens were found in the urological clinic, which accounted for 25.7% of the total number. Gram-negative bacteria predominated and its proportion was 59.23%. Gram-positive bacteria were isolated in 24.4%, and fungi were found in 16.37% of cases. The structure of pathogens isolated from stoma or obtained by catheterization was not significantly different. Most frequently isolated pathogens included @K. pneumonia (22.8%), @E. coli (21.2%), @C. albicans (17%), @P. aeruginosa (11%), @E. aerogenes (6%) and @S. aureus (3 %). @K. pneumonia usually had an unfavorable resistance pattern. E. coli isolated from urine samples had more favorable resistance pattern in comparison to pathogens obtained from stoma. The bacteria which were found in intensive care unit had the increased level of resistance. CONCLUSION: Gram-negative bacteria predominate in the urological clinic with a relatively high proportion of extended-spectrum beta-lactamase-producing organisms. Risk factors for the emergence of multi-resistant pathogens are the treatment in the intensive care unit and the presence of stomas or catheters. The PCR method, carried out in parallel with routine microbiological studies and regular analysis of the overall bacterial spectrum, allows to optimize the starting antibiotic therapy from the first day of the disease. The use of cephalosporins is not justified in the most cases. Aminoglycosides and fluoroquinolones remain effective. The use of either -Lactamase-protected penicillins or fosfomycin is possible only after obtaining the results of bacteriological study. When prescribing carbapenems, the risk of inefficiency is especially high in patients with stomas/catheters and transferred from the intensive care unit.

[Use of crizotinib for refractory ALK-positive lymphomas]. / Primenenie krizotiniba pri refrakternykh formakh ALK- pozitivnykh limfom.

AIM: To evaluate the safety and efficacy of crizotinib used in pediatric patients with relapsed or refractory ALK-positive anaplastic large-cell lymphoma (ALCL). SUBJECTS AND METHODS: The paper describes the experience with crizotinib used in 8 patients with refractory ALK-ALCL before and after allogeneic hematopoietic stem cell transplantation (HSCT). RESULTS: All the 8 (100%) patients treated with crizotinib were recorded to have complete responses, including complete metabolic ones (tumor disappearance as evidenced by positron emission tomography (PET)/computed tomography. CONCLUSION: Low and manageable toxicity of crizotinib and complete PET-negative responses in patients with resistant ALK lymphomas favor the need to test the drug as first-line therapy, by possibly decreasing the intensification of chemotherapy.

[Extrarenal rhabdoid tumor: A review of literature and a report of cases with atypical morphology]. / Ékstrarenal'naia rabdoidnaia opukhol'. Obzor literatury i opisanie sluchaev s netipichnoi morfologiei.

Extrarenal extracranial rhabdoid tumor (EERT) is a rare malignant pediatric tumor characterized by extremely aggressive behavior, rapid metastatic spread, low survival rates, and no targeted therapy. The morphological diagnosis of classical cases of EERT is not difficult and it is based on its characteristic histologic pattern and immunohistochemical findings in a relatively short time, which allows one to immediately initiate therapy. The paper describes two cases of ERRT in the complete absence of classical rhabdoid morphology, as revealed by light microscopy when the material was primarily assessed. The final diagnostic search could establish a diagnosis of EERT in both cases on the basis of immunohistochemical findings.

[All-Russian Consensus on Diagnosis and Treatment of Celiac Disease in Children and Adults]. / Vserossiiskii konsensus po diagnostike i lecheniyu tseliakii u detei i vzroslykh.

The paper presents the All-Russian consensus on the diagnosis and treatment of celiac disease in children and adults, which has been elaborated by leading experts, such as gastroenterologists and pediatricians of Russia on the basis of the existing Russian and international guidelines. The consensus approved at the 42nd Annual Scientific Session of the Central Research Institute of Gastroenterology on Principles of Evidence-Based Medicine into Clinical Practice (March 2-3, 2016). The consensus is intended for practitioners engaged in the management and treatment of patients with celiac disease. Evidence for the main provisions of the consensus was sought in electronic databases. In making recommendations, the main source was the publications included in the Cochrane Library, EMBASE, MEDLINE, and PubMed. The search depth was 10 years. Recommendations in the preliminary version were reviewed by independent experts. Voting was done by the Delphic polling system.

[Conditionally pathogenic microorganisms in patients with bisphosphonate jaw osteonecrosis].

The objective of the study was to define treatment strategy in cases of facial bones bisphosphonate induced osteonecrosis based on the study of the role of conditionally pathogenic oral microorganisms. Three typical clinical cases of bisphosphonate osteonecrosis of the facial bones were analyzed and 15 conditionally pathogenic oral microorganisms were identified in these patients using real-time PCR in saliva, wound and bone samples. A comparative analysis was carried out with purulent-inflammatory diseases of maxillofacial area. The study results proved an important role of conditionally pathogenic microorganisms of the oral cavity in the development of osteonecrosis of the facial bones. Wide range of bacterial species was identified in osteonecrosis of the facial bones patients. While bone tissue is most exposed to microbial communities, surgical treatment results in effective rehabilitation for a long period.

[ASSOCIATION OF POLYMORPHISM GENES OF SURFACTANT PROTEINS IN PATIENTS WITH INFLUENZA].

AIM: Evaluate role of gene polymorphisms of surfactant proteins in susceptibility and severity of influenza infection course in representatives of Moscow population. MATERIALS AND METHODS; 320 influenza patients, infected with various influenza virus strains, and 115 healthy individuals (control group),, were included into the study. Human DNA samples genotyping for determination of SFTPA2 gene rs1965708 and rs1059046, SFTPB gene rs1130866 polymorphisms was carried out using a modified method of "adjacent samples". RESULTS: Most of the individuals of the control group and influenza patients are carries of alleles and genotypes rs1965708 and rs1059046 of SFTPA2 gene, rs1130866 of SFTPB gene, that have, based on scientific literature data, shown association with severe course of influenza A(H1N1) pdm09 and other inflammatory diseases of the respiratory tract. Generally, significant differences in frequency of occurrence of unfavorable genotypes CC rs1965708, AA rs1059046 of SFTPA2 gene and CC rs1130866 of SFTPB gene in influenza patients in comparison with individuals of the control group were not detected, that gives evidence on a high (from 19 to 51%) prevalence of these genotypes in the studied population. Allele C and genotype CC rs1965708 of SFTPA2 gene, allele A and genotype AA rs1059046 of SFTPA2 gene, allele C and genotype CC rs1130866 of SFTPB gene did not shown an association with severe course of A(H1N1) pdm09 influenza. The following pathology registered in most (88%) of the patients with severe course of influenza A (H1N1)pdm09: diseases of cardiovascilar (44%), endocrine (36%) and respiratory (12%) systems. CONCLUSION: Because in most of the deceased patients due to severe course of A (H1N1)pdm09 influenza, diseases of cardiovascular, respiratory and endocrine system were detected, and an association of unfavorable disease outcome with the studied genetic markers was not detected, dominating risk factor of development of severe course and lethal outcome for A(H1N1)pdm09 influenza in the studied cohort was comorbidity.

Experimental investigation of pharmacodynamics and pharmacokinetics of carbamazepine nanoemulsion.

Anticonvulsant activity and pharmacokinetics of nanoemulsion and unmodified substance of carbamazepine were compared in experiments on mice. Carbamazepine nanoemulsion demonstrated significant anticonvulsant activity and was superior to unmodified substance of carbamazepine against seizures induced by maximum electric shock and picrotoxin. Relative bioavailability of carbamazepine after administration of nanoemulsion was 160% compared to unmodified substance. Carbamazepine nanoemulsion more effectively penetrated through BBB by 1.5 times in comparison with unmodified substance.

[Primary thyroid extranodal marginal zone lymphoma].

The paper gives the data available in the literature on the clinical and morphological features of thyroid lymphomas and on their diagnostic principles. The authors' observation details the histological and immunohistochemical characteristics of primary thyroid extranodal marginal zone lymphoma. The specific feature of the observation is total thyroid tissue substitution for tumor cells so the characteristic sign of chronic autoimmune thyroiditis were undetectable, but found only immunohistochemically from the remaining thyroid tissue follicle-like structures, which bears out the relationship between the development of lymphoma and autoimmune thyroiditis.

[Atypical teratoid/rhabdoid tumors of childhood].

The paper describes 6 cases of atypical teratoid/rhabdoid tumors (ATRT) in the complete absence of classical rhabdoid elements isolated from 25 INI1-negative central nervous system tumors investigated in the period 2006 to the present time. Analysis of the specific features of the histological structure of INI1-negative tumors could identify a few histological types of ATRT according to the conventionally standardized criteria for diagnostic search.

[Efficacy of anti-neuraminidase drugs application during and after an influenza pandemic].

The emergent 2009 A(H1N1) pandemic brought into acute focus the problem of choosing the most effective anti-influenza drugs for successive influenza infection spreading control. Oseltamivir and zanamivir, influenza virus neuraminidase inhibitors (NAIs), were recommended by the WHO experts for the treatment and prevention of influenza, including that caused by pandemic strains. A major concern regarding the use of specific antiviral compounds is the emergence of the drug-resistant strains. Oseltamivir carboxylate and zanamivir IC50 values were equal to 0.3-5.2 microM for the most of A(H1N1)pdm09 pandemic strains and 1.6-8.6 microM for the strains of influenza B virus in cell-based ELISA assay (2009-2010 season). All the studied strains of influenza A(H1N1 ) pdm09 (151) and B (22) viruses were sensitive to NAIs (2009-2011 seasons). For the first time in Russia oseltamivir-resistant A(H1N1) pdm09 influenza virus was isolated from the patient on the 5th day of a treatment course of this drug.

[The specific features of the cocirculation of influenza viruses in the 2010-2011 postpandemic period according to the results of activities of the D. I. Ivanovsky Research Institute of Virology, Ministry of Health and Social Development of Russia].

The paper gives the results of monitoring the circulation of influenza viruses in the 2010-2011 season, that covers the second year of circulation of pandemic A(H1N1)v virus strains, and their interaction with seasonal A (H3N2) and B strains. Unlike the previous season, the beginning of an increase in morbidity was recorded in January 2011; its peak in the most of contiguous areas was noted at 5-7 weeks of 2011, with its further decline to threshold levels at week 11 of 2011. Preschool and school children were most involved in the epidemic process. Three influenza virus strains (A(H1N1)v, A(H3N2), and B) were found to circulate. Differences were found in the level of participation of the isolated strains in individual areas of the Russian Federation. Detailed typing of the isolated strains determined the compliance of the vast majority of them with vaccine viruses. The pandemic influenza A(H1N1)v virus strains retained their susceptibility to oseltamivir and were resistant to rimantadine. The participation of non-influenza acute respiratory viral infection pathogens was estimated as follows: 11.9% for parainfluenza viruses, 5.9% for adenoviruses, and 3.5% for PC viruses, and 0.7% for pneumonia Mycoplasma, which was comparable with the previous epidemic seasons.

[Immunogenetics of type 1 diabetes mellitus--from fundamental ideas to medical practice].

The review of studies of Russian researchers on theoretical and practical aspects of genetic predisposition to type 1 diabetes associated with immunity: HLA and not HLA genes. Most important for practical public health outcomes are evidence that HLA-genetic predisposition to type 1 diabetes is associated with the DRB1-genotype, consisting entirely of variants DRB1-genes associated with the development of T1D. It was also established that CTLA4 gene has an independent predictive value for T1D.

[The development and testing of a molecular biological test system for DNA detection of anthrax pathogen by real-time polymerase chain reaction assay].

The paper presents the results of the development and testing of a molecular biological test system for DNA detection of anthrax pathogen (Bacillus anthracis) by real-time polymerase chain reaction assay. The test system has shown high sensitivity, specificity, and reproducibility of results of analysis, as exemplified by aqueous suspensions of daily agar cultures of Bacillus anthracis strains, related and heterologous species of microorganisms, and clinical materials of experimental animals. There is evidence for the persistence of the basic characteristics of the test system when stored at 22 +/- 2 degrees C for 12 months.